Tandospirone potentiates the fluoxetine-induced increases in extracellular dopamine via 5-HT1A receptors in the rat medial frontal cortex

Recent clinical studies suggest that 5-HT1A receptor agonists, including buspirone, may have an antidepressant effect and potentiate the efficacy of selective serotonin reuptake inhibitors (SSRI) in major depressive disorders. In the present study, we investigated the effect of tandospirone, a highly potent and selective 5-HT1A receptor agonist, on dopamine release and potentiation of fluoxetine-induced dopamine outflow in the medial frontal cortex using microdialysis in freely moving rats. Intraperitoneal injection of tandospirone (5 mg/kg) increased dopamine release to about 190% of basal levels. Pretreatment with the selective 5-HT1A receptor antagonist, WAY 100635 (1 mg/kg), blocked the effect of tandospirone. Local application of WAY 100635 (10 muM) via microdialysis probe antagonized the increase in dopamine release in the medial frontal cortex induced by systemic injection of tandospirone. Fluoxetine (10 mg/kg) also increased dopamine release in the medial frontal cortex, to 200% of basal levels, and the simultaneous administration of tandospirone and fluoxetine increased the release to 380%. These results indicate that tandospirone potentiates the fluoxetine-induced increase in dopamine release via 5-HT1A receptors in the rat medial frontal cortex, and suggest that tandospirone may have therapeutic potential for the treatment of depression. (C) 2002 Elsevier Science Ltd. All rights reserved.